P505: GIMEMA AML1819 TRIAL: GEMTUZUMAB OZOGAMICIN PLUS INTENSIVE CHEMOTHERAPY IMPACTS ON THE LEVEL OF POST-CONSOLIDATION MEASURABLE RESIDUAL DISEASE (MRD) IN ACUTE MYELOID LEUKEMIA
Authors: Adriano Venditti, Alfonso Piciocchi, Luca Maurillo, Maria Ilaria Del Principe, Raffaele Palmieri, Stefano Soddu, Federico Moretti, Prassede Salutari, Maurizio Martelli, Maria Paola Martelli, Mario Luppi, Alessandro Pulsoni, Francesco Zaja, Roberto Cairoli, Fabrizio Pane, Sergio Siragusa, Renato Bassan, Michela Rondoni, Milena Mirabile, Antonino Mulè, Germana Beltrami, Patrizia Zappasodi, Laura Cudillo, Andrea Mengarelli, Antonio Curti, Felicetto Ferrara, Giovanni Rossi, Ernesta Audisio, Giuseppina Spinosa, Alessia Tieghi, Monica Bocchia, Vincenza Martini, Catello Califano, Luigi Rigacci, Agostino Tafuri, Michele Gottardi, Paola Fazi, Marco Vignetti, Francesco Buccisano
Journal: HemaSphere (2023)

Background: Following the experience of the GIMEMA AML1310 protocol (Venditti A et al, Blood 2019), in which the choice between autologous (AuSCT) or allogeneic hematopoietic stem cell transplant (ASCT) was risk-adapted (for favorable- and adverse-risk categories) or MRD-driven (for patients in the intermediate-risk category), we designed a next generation, multicenter trial named AML1819 (NCT04168502). This trial recruits young patients (≤ 60 years of age) belonging to the ELN2017 favorable-and intermediate-risk categories, with the exception of cases FLT3 positive and relies on the addition of gemtuzumab ozogamicin (GO) to intensive chemotherapy (Castaigne S et al, Lancet 2012 – Lambert J et al, Haematologica 2019). AML1819 trial, likewise AML1310, is inspired to a MRD-oriented post-remission approach. Aims: The primary outcome measures of AML1819 are to determine (1) the percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO; (2) the efficacy of a post-transplant maintenance with glasdegib vs clinical observation in terms of disease free survival improvement. The present report illustrates the preliminary results of the post-consolidation MRD analysis. Methods: In AML1819, patients are to receive 1 induction and 1 consolidation with the addition of gemtuzumab ozogamicin (GO) and then, based on the level of post-consolidation MRD, they are submitted to an AuSCT (MRD neg) or ASCT (MRD pos). Following the transplant, the patients are randomized between observation or a maintenance with glasdegib, for 12 months. MRD is assessed by Reverse-Trascriptase quantitative-Polimerase Chain Reaction (RT-qPCR) for patients with a molecular marker (NPM1 mutation or CBF rearrangements) or by multiparametric flow cytometry (MFC) in those lacking a traceable molecular signature (Fig. n.1 Results: Of 171 patients enrolled, 145 patients (85%) are evaluable, median age 53 (18-61), 52% males and 48% females; 76 patients (52%) belonged to the ELN2017 favorable-risk (FR) category and 69 (48%) to the intermediate-risk (IR) one. Of 145 patients, 107 (74%) achieved a CR/CRi. In the FR and IR category, 63 of 76 (83%) and 44 of 69 (64%) achieved CR/CRi, respectively. Of 107 patients, 105 (98%) received the consolidation course and 96 (91%) [58 FR (60%) and 38 IR (40%)] are evaluable for post-consolidation MRD assessment. Overall, 74% (71) of 96 were MRD neg and 26% (25) MRD pos. When the analysis was split as per risk category, 81% (47) of 58 patients with FR AML became MRD neg after consolidation and 19% (11) were MRD pos. In the IR category, of 38 patients 63% (24) achieved a MRD neg status whereas 37% (14) remained MRD pos. The post-consolidation frequency of MRD negativity for patients belonging to the IR category of the AML1310 protocol was 46% (42 patients out of 92). With a median follow-up of 17.4 months, 1-year overall survival of FR and IR patients is 83.1% (SD 69.2%, 99.8%) and 72.1% (53.0%, 98.0%), respectively. Summary/Conclusion: In the AML1819 trial, the preliminary analysis of the MRD status after consolidation indicates that a remarkable proportion of patients become negative when GO is added to intensive chemotherapy. With all the limits of such a comparison, we also found that the proportion of patients being MRD negative after consolidation was higher in AML1819 trial than in AML1310 one, in which no GO was added to chemotherapy. Such a finding has practical implications since, in AML1819 trial, a lower fraction of patients is submitted to ASCT. These figures need confirmation in a more advanced phase of trial development, showing that the high frequency of MRD negativity translates into a survival benefit.Fig. 1. GIMEMA AML1819 Trial Design Keywords: Gemtuzumab ozogamicin, Acute myeloid leukemia, Chemotherapy, Measurable residual disease